Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	The structure of neurofibromin isoform 2 reveals different functional states.
Journal, issue, pages	Nature, Vol. 599, Issue 7884, Page 315-319, Year 2021
Publish date	Oct 27, 2021
Authors	Andreas Naschberger / Rozbeh Baradaran / Bernhard Rupp / Marta Carroni /
PubMed Abstract	The autosomal dominant monogenetic disease neurofibromatosis type 1 (NF1) affects approximately one in 3,000 individuals and is caused by mutations in the NF1 tumour suppressor gene, leading to ...The autosomal dominant monogenetic disease neurofibromatosis type 1 (NF1) affects approximately one in 3,000 individuals and is caused by mutations in the NF1 tumour suppressor gene, leading to dysfunction in the protein neurofibromin (Nf1). As a GTPase-activating protein, a key function of Nf1 is repression of the Ras oncogene signalling cascade. We determined the human Nf1 dimer structure at an overall resolution of 3.3 Å. The cryo-electron microscopy structure reveals domain organization and structural details of the Nf1 exon 23a splicing isoform 2 in a closed, self-inhibited, Zn-stabilized state and an open state. In the closed conformation, HEAT/ARM core domains shield the GTPase-activating protein-related domain (GRD) so that Ras binding is sterically inhibited. In a distinctly different, open conformation of one protomer, a large-scale movement of the GRD occurs, which is necessary to access Ras, whereas Sec14-PH reorients to allow interaction with the cellular membrane. Zn incubation of Nf1 leads to reduced Ras-GAP activity with both protomers in the self-inhibited, closed conformation stabilized by a Zn binding site between the N-HEAT/ARM domain and the GRD-Sec14-PH linker. The transition between closed, self-inhibited states of Nf1 and open states provides guidance for targeted studies deciphering the complex molecular mechanism behind the widespread neurofibromatosis syndrome and Nf1 dysfunction in carcinogenesis.
External links	Nature / PubMed:34707296 / PubMed Central
Methods	EM (single particle)
Resolution	2.9 - 4.8 Å
Structure data	13391 7pgp EMDB-13391, PDB-7pgp: The core structure of human neurofibromin isoform 2 Method: EM (single particle) / Resolution: 3.1 Å 13392 7pgq EMDB-13392, PDB-7pgq: GAP-SecPH region of human neurofibromin isoform 2 in closed conformation. Method: EM (single particle) / Resolution: 3.5 Å 13393 7pgr EMDB-13393, PDB-7pgr: The structure of human neurofibromin isoform 2 in closed conformation Method: EM (single particle) / Resolution: 4.0 Å 13394 7pgs EMDB-13394, PDB-7pgs: Consensus structure of human Neurofibromin isoform 2 Method: EM (single particle) / Resolution: 3.4 Å 13395 7pgt EMDB-13395, PDB-7pgt: The structure of human neurofibromin isoform 2 in opened conformation. Method: EM (single particle) / Resolution: 4.8 Å 13396 7pgu EMDB-13396, PDB-7pgu: Autoinhibited structure of human neurofibromin isoform 2 stabilized by Zinc. Method: EM (single particle) / Resolution: 3.3 Å EMDB-13397: The tip region of human Neurofibromin Isoform 2 stabilized by Zinc Method: EM (single particle) / Resolution: 2.9 Å EMDB-13398: The core region of human Neurofibromin Isoform 2 stabilized by Zinc. Method: EM (single particle) / Resolution: 3.1 Å EMDB-13399: The GAP-SecPH region of human Neurofibromin Isoform 2 stabilized by Zinc. Method: EM (single particle) / Resolution: 3.0 Å
Chemicals	ChemComp-PEV: (1S)-2-{[(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL STEARATE / POPE, phospholipidYM ChemComp-ZN: Unknown entry ChemComp-HOH*: WATER
Source	homo sapiens (human)
Keywords	SIGNALING PROTEIN / Neurofibromin / Cancer / GAP / Ras / Neurofibromatosis type 1